Estimating risk

Dr. Rizwanul Karim

Department of Epidemiology
Study Population
NEW TREATMENT
CURRENT
TREATMENT
DO NOT
IMPROVE
IMPROVE
DO NOT
IMPROVE
IMPROVE
Randomly Assigned
Defined Population
NOT EXPOSED EXPOSED
NO
DISEASE
DISEASE
NO
DISEASE
DISEASE
Not Randomly Assigned
People with
the disease
People without
the disease
Cases Controls
Start
With :
and
Then determine
Exposure History:
and
People without
the disease

Were
exposed
Were not
exposed

People with
the disease
Were
exposed
Were not
exposed

Cases Controls
Risk
Risk generally refers to the probability of some
untoward event.
Risk is the probability that people who are
exposed to certain risk factors will
subsequently develop a particular disease
more often than similar people who are not
exposed
Risk factors
Risk factor: Characteristics associated with an
increased risk of becoming diseased are called
risk factors.
Exposure : Exposure to a risk factor means
that a person, before becoming ill, has come
in contact with or has manifested the factor in
question.
The incidence of a disease in a population is termed
the absolute risk.

Absolute risk can indicate the magnitude of the risk in a
group of people with a certain exposure, but because it
does not take into consideration the risk of disease in
non-exposed individuals, it does not indicate whether
the exposure is associated with an increased risk of the
disease.
How do we determine whether a certain disease is
associated with a certain exposure
A food borne disease outbreak: Percent of people Sick among
those who ate and those who did not eat specific foods
Food Ate (% Sick) Did Not Eat ( % Sick )
Egg salad
83 30
Macaroni
76 67
Cottage cheese
71 69
Tuna salad
78 50
Ice cream
78 64
other
72 50
How do we determine whether a certain disease is
associated with a certain exposure
Food borne disease outbreak : Ways of calculating excess Risk
(A) (B) (C) (D)
Food Ate (% Sick) Did not Eat (% Sick) (A)/(B) (A) (B) (%)
Egg salad 83 30 2.77 53
Macaroni 76 67 1.13 9
Cottage cheese 71 69 1.03 2
Tuna salad 78 50 1.56 28
Ice cream 78 64 1.21 14
other 72 50 1.44 22
Determining excess risk
One approach, is to calculate the ratio of the attack
rate in those who ate each food to the attack rate in
those who did not eat the food.
An alternate approach for identifying any excess risk
in exposed individuals is to subtract the risk in those
who did not eat the food from the risk in those who
did eat the food.
The difference represents the excess risk in those who
were exposed.
Measuring excess risk
whether a certain exposure is associated with
a certain disease, we must determine whether
there is an excess risk of disease in exposed
populations by comparing the risk of disease
in exposed populations to the risk of disease
in non-exposed populations.

Ways to express and compare risk
Measures of Effect
Expression Question Definition
Absolute Risk What is the incidence of disease in
a group initially free of condition?
Attributable risk
( Risk difference )
What is the incidence of disease
Attributable to Exposure


Relative Risk
(Risk ratio)
How many times more likely are
exposed persons to become
diseased, relative to non-exposed
persons


group in the people of #
time of period given a over cases new of #
= I
E
E
I I AR =
E
E
I
I
RR =
Ways to express and compare risk
Measures of Effect
Expression Question Definition
Population attributable risk What is the incidence of disease in a
population, associated with the
prevalence of a risk factor (exposure)
Population attributable
fraction
What fraction of disease in a
population is attributable to
exposure to a risk factor?


P AR AR
P
* =
T
P
P
I
AR
AF =
Where = Incidence in Exposed persons, = Incidence in the Non-Exposed
persons; = Prevalence of Exposure to a risk factor; and = Total incidence of disease
in a population .

E
I
E
I
T
I
P
Calculating measures of effect: Cigarette smoking and
Death from lung cancer
Death rate (absolute risk) from lung cancer in smokers 0.96/1000/year
Death rate (absolute risk) of cancer in cigarette non-smokers 0.07/1000/year
Prevalence of cigarette smoking 56%
Total death rate from lung cancer 0.56/1000/year

Compared Risk

Attributable risk = 0.96/1000/year 0.07/1000/year = 0.89/1000/year
Relative risk = 0.96/1000/year 0.07/1000/year = 13.7
Population-attributable risk = 0.89/1000/year X 0.56 = 0.50/1000/year
Population attributable fraction = 0.50/1000/year 0.56/1000/year = 0.89

An excess risk can be calculated in the
two following ways:

The ratio of the risks (or of the incidence rates):



The difference in the risks (or in the incidence
rates):


exposed - non in the risk Disease
exposed in risk Disease
exposed) - non in risk disease exposed in risk (disease
Measuring risk
An Example Comparing two way of calculating excess risk
POPULATION
(A) (B)
Incidence (%)
In exposed 40 90
In non-exposed 10 60
Difference in incidence rates 30 30
Ratio of incidence rates 4.0 1.5
The Concept of Relative Risk


If we carry out a cohort study
the ratio of the risk of disease in exposed
individuals to the risk of disease in non-exposed
individuals? is called the relative risk.

Relative risk =






exposed - non in Risk
exposed in Risk
Relative risk
The relative risk can also be defined as the
probability of an event (developing a disease)
occurring in exposed people compared to the
probability of the event in non-exposed
people, or as the ratio of the two probabilities.

How do we interpret the value of a relative risk?
There are three possibilities
Interpreting Relative Risk (RR) of a Disease
If RR = 1 Risk in exposed equal to risk in non-exposed
(no association)
If RR > 1 Risk in exposed greater than risk in non-
exposed (positive association; possibly causal)
If RR < 1 Risk in exposed less than risk in non-exposed
(negative association; possibly protective)
Relative risk
Risk calculation in a cohort study
Then follow to see whether
Disease
develop
Disease does
not develop
totals Incidence
rates of
disease

First
select
exposed a b a + b
Not exposed c d c + d
= Incidence in exposed = Incidence in non-exposed
b a
a
+
d c
c
+
b a
a
+ d c
c
+

Relative risk =









Relative risk =

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=
d c
c
b a
a
exposed - non in Incidence
exposed in Incidence
Smoking and coronary heart disease ( CHD): A hypothetical cohort study of
3,000 cigarette smokers and 5,000 nonsmokers
CHD develops CHD does not
develop
Totals Incidence per
1000 /year
Smoke
cigarettes
84 2916 3,000 28.0
Do not smoke
cigarettes
87 4913 5,000 17.4
61 . 1
4 . 17
0 . 28
exposed - non in Incidence
exposed in Incidence
= =
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+
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+
=
d c
c
b a
a
Odds
Odds, is the ratio of two probabilities,pthe
probability of an event) to that of (1-p)1-
the probability of the event.
Odds and probability contain the same
information, but they express it differently:
Odds = probability of an event /(1- the
probability of the event)
Probability = Odds / (1+ Odds)
The Odds Ratio (Relative Odds)
In a case-control study, however, we do not know the
incidence in the exposed population or the incidence in the
non-exposed population because we start with diseased
people (cases) and non-diseased people (controls).

Hence, in a case-control study we cannot calculate the relative
risk directly. We shall see how another measure of
association, the odds ratio, can be obtained from either a
cohort or a case-control study and can be used instead of the
relative risk.
we have learned,
the proportion of the exposed population in whom
disease develops and
the proportion of the non-exposed population in
whom disease develops
in a cohort study.

Similarly, in case-control studies, we have discussed
the proportion of the cases(occurrence of disease)
who were exposed and
the proportion of the controls(non-occurrence of
disease) who were exposed
Defining the Odds Ratio in Cohort and in Case-
Control Studies
Suppose we are betting on a horse named Epi Beauty, which has a
60% probability of winning the race (P).
Epi Beauty therefore has a 40% probability of losing (1 - P).

If these are the probabilities, what are the odds that the horse will win
the race?

the odds of an event can be defined as the ratio of the number of
ways the event can occur to the number of ways the event cannot
occur.
Measuring odds



It is important to keep in mind the distinction between
probability and odds.
Probability of winning = 60%

Odds of winning =

5 . 1
% 40
% 60
1
race the lose l Beauty wil Epi y that Probabilit
race win the l Beauty wil Epi y that Probabilit
=

=
=
or
p
p
odds
odds
5 . 1
% 40
% 60
=
Odds = probability of an event /
(1- the probability of the event)
= 60/40 = 1.5

Probability = Odds / (1+ Odds)
= 1.5/(1+1.5) = .6

The odds that the disease will develop in an exposed person ,looking
only at the top row in which we see that there are (a + b) exposed
persons; the odds that the disease will develop in them are a:b
Or .
The probability (P) that the disease will develop in an exposed person,
is the incidence of the disease in the top row (exposed persons),
which equals .
b
a
b a
a
+
Recall From the Epi Beauty example.)
Similarly, there are (c + d) non-exposed persons; the probability that the
disease will develop in non-exposed persons is
and the odds of the disease developing in these non-exposed persons
are c:d or .
p
p
1
d c
c
+
d
c
Odds ratio in cohort study
Odds ratio in Cohort studies
In a cohort study, to answer the question of whether there is
an association between the exposure and the disease, we can
either use the relative risk or we can use the odds ratio (also
called the relative odds).
In a cohort study, the odds ratio is defined as the ratio of the
odds of development of disease in exposed persons to the
odds of development of disease in non-exposed persons, and

it can be calculated as
bc
ad
d
c
b
a
=
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Odds ratio in a Cohort study
Develop
disease
Do not
develop
Disease
Exposed
a b
Not Exposed
c d
bc
ad
d
c
b
a
= =
disease develops person exposed - non an that Odds
disease develops person exposed an that Odds
Odds ratio in a case control study
Calculation of Proportions Exposed in a Case-Control study
First select
Cases ( with disease) Controls(without
disease)
Then Measure
The Exposure
Were exposed
a b
Were not exposed
c d
totals a + c b + d
Proportion exposed

c a
a
+ d b
b
+
Odds ratio in a Case-control study
Cases
(with
disease)
Control
(without
disease)
History of
Exposure
a b
No history
Of Exposure
c d
bc
ad
d
b
c
a
= =
exposed was control a that odds
exposed was case a that Odds
In a case-control study, we cannot calculate the relative
risk directly to determine whether there is an
association between the exposure and the disease.

This is because, having started with cases and
controls rather than with exposed and non-exposed
persons, we do not have information about the
incidence of disease in exposed versus non-
exposed persons.

However, we can use the odds ratio as a measure of
the association between exposure and disease in a
case-control study,


The odds of a case having been exposed are a:c or


The odds of a control having been exposed are b:d or

in a case-control study, is defined as the ratio of the odds
that the cases were exposed to the odds that the
controls were exposed. This is calculated as follows:
.
bc
ad
d
b
c
a
=
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c
a
d
b
The odds ratio or the cross-products ratio can be viewed as the ratio
of the product of the two cells that support the hypothesis of an
association

(cells a and d- diseased people who were
exposed and non-diseased people who were not
exposed),

to the product of the two cells that negate the hypothesis of an
association

(cells b and c-non-diseased people who were
exposed and diseased people who were not
exposed).
When Is the Odds Ratio a Good Estimate of the
Relative Risk?
When is the odds ratio (relative odds) obtained in a case-
control study a good approximation of the relative risk in the
population? When the following three conditions are met:
When the cases studied are representative, with regard to
history of exposure, of all people with the disease in the
population from which the cases were drawn.
When the controls studied are representative, with regard to
history of exposure, of all people without the disease in the
population from which the cases were drawn.
When the disease being studied does not occur frequently.

Recall that there are a + b exposed persons. Because most diseases with
which we are dealing occur infrequently, very few persons in an exposed
population will actually develop the disease; consequently,

a, is very small compared to b, and one can
approximate a + b as b, or (a + b) b.
Similarly, very few non-exposed persons (c + d) develop the
disease, and we can approximate c + d as d, or (c + d) d.





Therefore, we may calculate a relative risk as follows:
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=
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+
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+
d
c
b
a
d c
c
b a
a
Disease
develop
Do not Develop
Disease
Exposed 200 9,800 10,000
Not
exposed
100 9,900 10,000
2
000 , 10 / 100
000 , 10 / 200
=
The Odds ratio is a good estimate of the relative risk when a
disease is infrequent


Relative risk =



Odds ratio =
02 . 2
800 , 9 100
900 , 9 200
=
X
X
Disease
develop
Do not Develop
Disease
Exposed 50 50 100
Not
exposed
25 75 100
2
100 / 25
100 / 50
=
The Odds ratio is not a good estimate of the relative risk when
a disease is not infrequent


Relative risk =



Odds ratio =
3
50 25
75 50
=
X
X
REMEMBER


1. The relative odds (odds ratio) is a useful measure of
association, in and of itself, in both case-control and
prospective studies.

2. In a cohort study, the relative risk can be calculated
directly.

3. In a case-control study, the relative risk cannot be
calculated directly, so that the relative odds or odds
ratio (cross-products ratio) is used as an estimate of
the relative risk when the risk of the disease is low.
CALCULATING THE ODDS RATIO IN AN UNMATCHED CASE-
CONTROL STUDY
Cases Controls
E N
E E
N N
E N
N E
N N
E N
E E
E N
N N
E = Exposed
N = Not Exposed
Let us assume that this case-control study is done without any
matching of controls to cases.
Thus, 6 of the 10 cases were exposed and
3 of the 10 controls were exposed.
If we arrange these data in a 2 2 table, we obtain the following:
Cases Controls
Exposed 6 3
Non-exposed 4 7
Total 10 10
Measuring odds ratio in unmatched pair
The odds ratio in this unmatched study equals
the ratio of the cross-products:

5 . 3
12
42
3 4
7 6
ratio Odds
ratio Odds
= = =
=
X
X
bc
ad
Example of calculating an Odds Ratio from a case control Study
First select
CHD Cases Controls
Then Measure
Past Exposure
Smokers
Non-Smokers
Totals 200 (a + c) 400 (b + d)
Proportions of Smoking Cigarette 56%
44%

Odds ratio

112 (a) 176 (b)
88 (c) 224 (d)
62 . 1
88 176
224 112
= =
X
X
bc
ad
Calculating Odds ratio
Calculating the odds ratio in a matched pairs
case-Control study
In selecting the study population in case-control studies, controls are
often selected by matching each control to a case according to variables
that are known to be related to disease risk, such as sex, age, or race
(individual matching or matched pairs).

The results are then analyzed in terms of case-control pairs rather than
for individual subjects.
If exposure is dichotomous (a person is either exposed or not exposed),
only the following four types of case-control pairs are possible:
Concordant pairs 1. Pairs in which both the case and the control were exposed a
2. Pairs in which neither the case nor the control was exposed d
Discordant pairs 3. Pairs in which the case was exposed but the control was not b
4. Pairs in which the control was exposed and the case was not c
Control
Exposed Not-Exposed

Cases
Exposed
a b
Not-Exposed
c d
The odds ratio for matched pairs is therefore the ratio of the discordant
pairs (i.e., the ratio of the number of pairs in which the case was exposed
and the control was not, to the number of pairs in which the control was
exposed and the case was not).

Odds ratio (matched pairs ) =
c
b
The concordant pairs (a and d, in which cases and controls were either both
exposed or both not exposed) are ignored, because
they do not contribute to our knowledge of how cases and controls differ
in regard to past history of exposure.
CALCULATING THE ODDS RATIO IN AN UNMATCHED CASE-
CONTROL STUDY
Cases Controls
E N
E E
N N
E N
N E
N N
E N
E E
E N
N N
E = Exposed
N = Not Exposed
= Matched
Control
Exposed Not-Exposed
Cases
Exposed
Not-Exposed
2,a 4,b
1,c 3,d
Pairs in which the case was
exposed but the control was
not b

Pairs in which the control
was exposed and the case
was not c
There are four pairs in which the
case was exposed and the control
was not and one pair in which the
control was exposed and the case
was not.


4
1
4
ratio Odds = = =
c
b
Attributable Risk for the Exposed Group
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group exposed - non
in Incidence
group exposed
in Incidence
The relative risk is important as a measure of the strength of the
association, a major consideration in deriving causal inferences.

How much of the disease that occurs can be attributed to a certain exposure?

This is answered by another measure of risk,
The attributable risk, which is defined as the amount or proportion of
disease incidence (or disease risk) that can be attributed to a specific
exposure.
Attributable Risk for the Exposed Group
Every person shares the background risk regardless of whether or not he or
she has had the specific exposure in question (in this case, smoking) .
Thus, both non-exposed and exposed persons have this background risk.

Therefore, the total risk of the disease in exposed individuals is the sum of the
background risk that any person has and the additional risk due to the
exposure in question.

If we want to know how much of the total risk in exposed persons is due to the
exposure, we should subtract the background risk from the total risk

Because the risk in the non-exposed group is equal to the background risk, we
can calculate the risk in the exposed group that is a result of the specific
exposure by subtracting the risk in the non-exposed group (the background
risk) from the total risk in the exposed group.
Incidence attributable to Exposure and incidence not
attributable to exposure
L
e
v
e
l

o
f

R
i
s
k

In exposed
group
In non-exposed
group
L
e
v
e
l

o
f

R
i
s
k

In exposed
group
In non-exposed
group
Background
Risk
L
e
v
e
l



o
f




R
i
s
k

In exposed
group
In non-exposed
group
{
{
Incidence due to
Exposure
Incidence not
due to Exposure
Estimating the potential for prevention
group exposed in Incidence
group exposed - non
in Incidence
group exposed
in Incidence
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what proportion of the risk in exposed persons is due to the
exposure?
We could then express the attributable risk as
the proportion of the total incidence in the exposed group
that is attributable to the exposure by simply dividing the
previous formula by the incidence in the exposed group, as
follows:
Attributable risk-potential for prevention
The attributable risk expresses the most that we can hope to
accomplish in reducing the risk of the disease if we completely
eliminate the exposure.

For example, if all smokers were induced to stop smoking, how much of
a reduction could we anticipate in lung cancer rates?

From a practical programmatic standpoint, the attributable risk may be
more relevant than the relative risk.

The relative risk is a measure of the strength of the association and the
possibility of a causal relationship, but the attributable risk indicates the
potential for prevention if the exposure could be eliminated.
Attributable Risk for the total population population
attributable risk
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risk) d (backgroun
group exposed - non
in Incidence
population total
in Incidence
If we want to calculate the attributable risk in the total population, the
calculation is similar to that for exposed people, but we begin with
the incidence in the total population and again subtract the
background risk, or the incidence in the non-exposed population.
The incidence in the total population that is due to the exposure* can be
calculated as shown in formula
*Incidence in the population due to the Exposure =
Attributable risk for the Exposed group X Proportion of the population exposed
Population attributable risk
population in total Incidence
group exposed - non
in Incidence
population total
in Incidence
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The attributable risk for the total population is a valuable concept for the public
health worker. If smoking were eliminated, what proportion of the incidence of
lung cancer in the total population (which consists of both smokers and
nonsmokers) would be prevented? The answer is: the attributable risk in the
total population [ population attributable risk PAR]

This is often both the critical issue and the question that is raised by policy-
makers and by those responsible for funding prevention programs. if all smokers
in the community stopped smoking, what would the impact of this change be on
the incidence of lung cancer in the total community population (which includes
both smokers and nonsmokers)?
Attributable risk example
Smoking and Coronary heart disease (CHD) : A hypothetical Cohort of 3,000
cigarette Smokers and 5,000 Nonsmokers
CHD Develop CHD does not develop Total Incidence/thousand/year
Smoke
cigarette
84 2,916 3,000 28.0
Do not smoke
cigarette
87 4,913 5,000 17.4

Incidence among Smokers =


Incidence among non-Smokers =
thousand / 28
3000
84
=
thousand / 4 . 17
5000
87
=
Attributable risk- amount
000 , 1
6 . 10
000 , 1
4 . 17 28
group exposed - non
in Incidence
group exposed
in Incidence
=

=
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Attributable risk- proportion
% 9 . 37 379 . 0
0 . 28
6 . 10
0 . 28
4 . 17 0 . 28
group exposed in Incidence
group exposed - non
in Incidence
group exposed
in Incidence
= = =

=
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Incidence in total population
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risk) d (backgroun
group exposed - non
in Incidence
population total
in Incidence
( ) ( )
000 , 1
1 . 22
56 .
000 , 1
4 . 17
44 . 0
000 , 1
0 . 28
population in
smokers - non %
smokers - non
in Incidence
population in
smokers %
smokers in
Incidence
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we know that the incidence among the smokers is 28.0 per 1,000 and
the incidence among the nonsmokers is 17.4 per 1,000. However, we
do not know the incidence in the total population. Let us assume that,
from some other source of information, we know that the proportion of
smokers in the population is 44% (and therefore the proportion of
nonsmokers is 56%).
Population attributable risk- amount
000 , 1
7 . 4
000 , 1
4 . 17
000 , 1
1 . 22
group exposed - non
in Incidence
population total
in Incidence
= =
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Population attributable risk- amount*
Population attributable risk

Attributable risk X Prevalence of exposure in the
population
= ( 10.6 X .44)
= 4.66
= 4.7/ 1000 population
Population attributable risk- proportion
% 3 . 21
1 . 22
4 . 17 1 . 22
population in total Incidence
group exposed - non
in Incidence
population total
in Incidence
=

=
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Question-1
In an epidemiological study for examining the relationship
between developmental disorders and prenatal exposure to
cocaine, the hospital records of 1000 infants diagnosed with a
developmental disorder and 1000 infants attended for other
disease were inspected. Of the 1000 children with a
developmental disorder, 800 were born to mothers known to
have abused cocaine during their pregnancy , compared to
300 of the comparison group infants.
what is the study design the researcher adopted here and
what is the measure of effect of cocaine abuse?
Question-2
One hundred children known to have been exposed to high
levels of lead during the first 12 months of life were followed
for 15 years ; 40 developed an affective disorder. A similar
group of 100 children who were not exposed to high levels of
lead during the first 12 months of life were also followed over
the same time period; 5 of the children developed an
affective disorder.
Find out the relationship between high lead exposure and
affective disorder. If we were be able to remove the
exposure at their first year of life, what proportion of children
could be out of the disorder?
Question-3
To study the possible association between oral
contraceptive use and occurrence of rheumatoid arthritis
(RA) , an investigator selected 100 women with confirmed
diagnosis of RA and 200 women undergoing treatment in
the same hospital for other conditions . Forty percent of the
RA patients gave history of oral contraceptive use whereas
40% of the women of other conditions were non-users .
what type of study design was employed and estimate the
risk of developing RA from oral contraceptive use.